Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression.
Tumor necrosis factor alpha (TNF-alpha) is an immunoregulatory cytokine capable of inducing viral expression in cells chronically infected with the human immunodeficiency virus (HIV), such as the promonocytic line U1 and the T-lymphocytic line ACH-2. In the present study, we demonstrate an autocrine mechanism of TNF-alpha-mediated HIV induction. Stimulation of U1 and ACH-2 cells with phorbol 12-myristate 13-acetate (PMA) resulted in the induction of TNF-alpha mRNA and the secretion of TNF-alpha. Of note is the fact that anti-TNF-alpha antibodies significantly suppressed the expression of HIV in PMA-stimulated U1 and ACH-2 cells. Furthermore, anti-TNF-alpha antibodies also suppressed both the constitutive and inducible levels of viral expression in the chronically infected promonocytic clone U33.3. This study illustrates the interrelationship between the regulation of HIV expression and normal immunoregulatory mechanisms in that virus expression, both constitutive and induced, can be modulated by an autocrine pathway involving TNF-alpha, a cytokine involved in the complex network of regulation of the normal human immune response.
Poli
G
G
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Kinter
A
A
Justement
J S
JS
Kehrl
J H
JH
Bressler
P
P
Stanley
S
S
Fauci
A S
AS
D000906:Antibodies; D000911:Antibodies, Monoclonal; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects
D000906:Antibodies; D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate